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Mercaptopurine Therapy in Ulcerative Colitis (OPTIC)

Primary Purpose

Colitis, Ulcerative

Status
Unknown status
Phase
Phase 3
Locations
Netherlands
Study Type
Interventional
Intervention
Mercaptopurine (Purinethol)
Placebo
Mesalamine
Prednisone
Sponsored by
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Colitis, Ulcerative focused on measuring Therapeutic Drug Monitoring, Mercaptopurine (6-MP), Thiopurine, Efficacy

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Confirmed diagnosis of UC by endoscopy and histopathology
  2. Patients between 18 and 80 years of age
  3. Active disease, despite oral treatment with at least 2g/day 5-ASA
  4. Treatment with oral corticosteroids is required

Exclusion Criteria:

  1. Prior treatment with thiopurines
  2. Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab)
  3. Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician)
  4. Chronic Obstructive Pulmonary Disease (COPD)
  5. Acute coronary heart disease
  6. (Bacterial) gastroenteritis has to be treated first
  7. Coagulation disorders
  8. Active malignancy
  9. History of colonic dysplasia/cancer
  10. Extensive colonic resection, i.e. subtotal colectomy with <15 cm colon in situ
  11. Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics.
  12. Known systemic fungal infections or parasitic infections have to be treated first
  13. Known duodenal or ventricular ulcus
  14. Substance abuse, such as alcohol (> 80 gram/day - one standard glass contains 10 gram of alcohol), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded
  15. Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician)
  16. Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening.
  17. Leucopenia (Neutrophil count < 1,8x10^9/L)
  18. Thrombopenia (Platelets < 90x10^9/L)
  19. Elevated liver enzymes (>2x ULN)
  20. Abnormal renal function (eGFR< 30 mL/min)
  21. Other conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedure

Sites / Locations

  • Noordwest ZiekenhuisgroepRecruiting
  • FlevoziekenhuisRecruiting
  • Meander MCRecruiting
  • Amsterdam UMC, location VUMCRecruiting
  • OLVG OostRecruiting
  • Amsterdam UMC, location AMCRecruiting
  • Amstelland HospitalRecruiting
  • MC HaaglandenRecruiting
  • Tergooi HospitalRecruiting
  • WestfriesgasthuisRecruiting
  • St. Antonius HospitalRecruiting
  • Sint Franciscus GasthuisRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Mercaptopurine (Purinethol)

Placebo

Arm Description

Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.

Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.

Outcomes

Primary Outcome Measures

Clinical and endoscopic remission
Defined as a SCCAI-score ≤ 4, a UCEIS-score ≤ 3 and a total Mayo score ≤ 2, with no individual subscore >1.

Secondary Outcome Measures

(Serious) Adverse Events
Occurrence of (serious) adverse events ((S)AE)
Leukocyte counts
Liver function tests
Occurrence of subjective thiopurine intolerance
6-TGN levels
6-MMP levels
Occurrence of treatment failure
Occurrence of upscaling treatment
Occurrence of upscaling treatment to biologicals (anti-TNF agents or vedolizumab)
Treatment costs
Budget-impact analysis and cost-utility analysis

Full Information

First Posted
September 9, 2016
Last Updated
January 6, 2020
Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development
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1. Study Identification

Unique Protocol Identification Number
NCT02910245
Brief Title
Mercaptopurine Therapy in Ulcerative Colitis
Acronym
OPTIC
Official Title
Efficacy of Optimized Thiopurine Therapy in Ulcerative Colitis (OPTIC)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
November 2016 (Actual)
Primary Completion Date
April 30, 2022 (Anticipated)
Study Completion Date
April 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborators
ZonMw: The Netherlands Organisation for Health Research and Development

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This project is a double-blind, randomized, placebo-controlled, multicenter trial in the Netherlands. The aim of this study is to investigate the therapeutic efficacy of optimized 6-mercaptopurine (6-MP) in ulcerative colitis patients. Therapeutic drug monitoring (TDM) will be performed in order to optimize treatment outcomes and objective endoscopic endpoints will be used.
Detailed Description
Subjects will receive treatment with oral prednisone 40 mg/day for 2 weeks, followed by fixed tapering over 6 weeks. Half of the subjects will be randomized to concomitant 6-MP 1-1.5 mg/kg/day and half will receive concomitant placebo treatment. During the entire course of the trial all subjects will receive maintenance treatment with 5-ASA in an oral dose of at least 2 gram per day. Subjects will be subjected to one colonoscopy at baseline and one sigmoidoscopy in week 52 in order to assess endoscopic disease activity. Data will be collected using electronic case report forms (eCRF) with Castor EDC. Quality and data validation procedures will be applied to ensure the validity and accuracy of the clinical database. Monitoring of the study will be done according to the GCP guidelines and following a monitoring plan. The financier of the study, ZonMw Goed Gebruik Geneesmiddelen, has the right to perform an audit if seen necessary.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colitis, Ulcerative
Keywords
Therapeutic Drug Monitoring, Mercaptopurine (6-MP), Thiopurine, Efficacy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
136 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mercaptopurine (Purinethol)
Arm Type
Active Comparator
Arm Description
Mercaptopurine (Purinethol),1-1.5 mg/kg/day oral, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, 1-1.5 mg/kg/day, 52 weeks & Prednisone, 40 mg/day oral, 2 weeks, followed by fixed tapering over 6 weeks OR budesonide (cortiment) 9 mg/day during 8 weeks & Mesalamine, 2 g/day oral, 52 weeks.
Intervention Type
Drug
Intervention Name(s)
Mercaptopurine (Purinethol)
Other Intervention Name(s)
Purinethol
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Mesalamine
Other Intervention Name(s)
Asacol, Mezavant, Pentasa, Salofalk
Intervention Type
Drug
Intervention Name(s)
Prednisone
Primary Outcome Measure Information:
Title
Clinical and endoscopic remission
Description
Defined as a SCCAI-score ≤ 4, a UCEIS-score ≤ 3 and a total Mayo score ≤ 2, with no individual subscore >1.
Time Frame
After 52 weeks of treatment
Secondary Outcome Measure Information:
Title
(Serious) Adverse Events
Description
Occurrence of (serious) adverse events ((S)AE)
Time Frame
Continue during 52 weeks of treatment
Title
Leukocyte counts
Time Frame
Every 6 weeks during 52 weeks of treatment
Title
Liver function tests
Time Frame
Every 6-12 weeks during 52 weeks of treatment
Title
Occurrence of subjective thiopurine intolerance
Time Frame
Every 6-12 weeks during 52 weeks of treatment
Title
6-TGN levels
Time Frame
Every 6-12 weeks during 52 weeks of treatment
Title
6-MMP levels
Time Frame
Every 6-12 weeks during 52 weeks of treatment
Title
Occurrence of treatment failure
Time Frame
Continue during 52 weeks of treatment
Title
Occurrence of upscaling treatment
Description
Occurrence of upscaling treatment to biologicals (anti-TNF agents or vedolizumab)
Time Frame
Continue during 52 weeks of treatment
Title
Treatment costs
Description
Budget-impact analysis and cost-utility analysis
Time Frame
Every 3 months during 52 weeks of treatment
Other Pre-specified Outcome Measures:
Title
Disease specific quality of life
Description
Quality of life measured by use of the IBD questionnaire (IBDQ)
Time Frame
Every 3 months during 52 weeks of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed diagnosis of UC by endoscopy and histopathology Patients between 18 and 80 years of age Active disease, despite oral treatment with at least 2g/day 5-ASA Treatment with oral corticosteroids is required Exclusion Criteria: Prior treatment with thiopurines Prior treatment with biologics (e.g. anti-TNF agents and vedolizumab) Current pregnancy (a pregnancy test will be performed if necessary according to the treating physician) Chronic Obstructive Pulmonary Disease (COPD) Acute coronary heart disease (Bacterial) gastroenteritis has to be treated first Coagulation disorders Active malignancy History of colonic dysplasia/cancer Extensive colonic resection, i.e. subtotal colectomy with <15 cm colon in situ Concomitant therapy with drugs interfering with MP metabolism, like allopurinol, ribavirin or anti-epileptics. Known systemic fungal infections or parasitic infections have to be treated first Known duodenal or ventricular ulcus Substance abuse, such as alcohol (> 80 gram/day - one standard glass contains 10 gram of alcohol), I.V. drugs and inhaled drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years. Subjects receiving methadone within the past 2 years are also excluded Positive tuberculosis screen (when a screening is performed at the discretion of the treating physician) Active hepatitis B virus or hepatitis C virus infection defined as a positive anti-HCV, HBsAg and/or anti-HBcore screening. Leucopenia (Neutrophil count < 1,8x10^9/L) Thrombopenia (Platelets < 90x10^9/L) Elevated liver enzymes (>2x ULN) Abnormal renal function (eGFR< 30 mL/min) Other conditions which in the opinion of the investigator may interfere with the subject's ability to comply with the study procedure
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mark Löwenberg, MD, PhD
Phone
+31205667621
Email
m.lowenberg@amc.uva.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Sara van Gennep, MD
Phone
+31205668708
Email
s.vangennep@amc.uva.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark Löwenberg, MD, PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Noordwest Ziekenhuisgroep
City
Alkmaar
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dirk van Asseldonk, MD PhD
Email
dp.van.asseldonk@nwz.nl
Facility Name
Flevoziekenhuis
City
Almere
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marco Mundt
Email
mmundt@flevoziekenhuis.nl
Facility Name
Meander MC
City
Amersfoort
ZIP/Postal Code
3813 TZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bindia Jharap, MD, PhD
Email
b.jharap@meandermc.nl
Facility Name
Amsterdam UMC, location VUMC
City
Amsterdam
ZIP/Postal Code
1081 HZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nanne de Boer, MD, PhD
Email
khn.deboer@vumc.nl
First Name & Middle Initial & Last Name & Degree
Sara van Gennep, MD
Phone
+31205667805
Email
s.vangennep@amc.uva.nl
Facility Name
OLVG Oost
City
Amsterdam
ZIP/Postal Code
1090 HM
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
JM Jansen, MD
Email
j.m.jansen@olvg.nl
Facility Name
Amsterdam UMC, location AMC
City
Amsterdam
ZIP/Postal Code
1105AZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Löwenberg, MD, PhD
Phone
+31205667621
Email
m.lowenberg@amc.uva.nl
First Name & Middle Initial & Last Name & Degree
Sara van Gennep, MD
Phone
+31205667805
Email
s.vangennep@amc.uva.nl
Facility Name
Amstelland Hospital
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M. Gielen, MD
Email
margi@zha.nl
Facility Name
MC Haaglanden
City
Den Haag
ZIP/Postal Code
2512 VA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nidhi Srivastava, MD
Email
n.srivastava@mchaaglanden.nl
Facility Name
Tergooi Hospital
City
Hilversum
ZIP/Postal Code
1213 XZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Itta M Minderhoud
Email
iminderhoud@tergooi.nl
First Name & Middle Initial & Last Name & Degree
Jan van den Brande
Email
jvandenbrande@tergooi.nl
Facility Name
Westfriesgasthuis
City
Hoorn
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
X.G. Vos, MD, PhD
Email
X.G.Vos@westfriesgasthuis.nl
Facility Name
St. Antonius Hospital
City
Nieuwegein
ZIP/Postal Code
3435 CM
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Petra van Boeckel, MD
Email
p.van.boeckel@antoniusziekenhuis.nl
Facility Name
Sint Franciscus Gasthuis
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
R. West
Email
R.West@Franciscus.nl

12. IPD Sharing Statement

Plan to Share IPD
No

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Mercaptopurine Therapy in Ulcerative Colitis

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